Phase I/II trial of recombinant human interleukin-11 treatment following ICE in young patients with solid tumours or lymphoma

Thrombocytopenia remains the major dose-limiting toxicity of myelosuppressive chemotherapy in children with solid tumours. The Food and Drug Administation (FDA) has approved human interleukin-11 (rhIL-11) as a treatment of solid tumours and lymphomas with severe chemotherapy-induced thrombocytopenia in adults.

In this phase I/II trial, researchers examined using human-interleukin-11 to treat solid tumours and lymphomas in children, adolescents and young children following treatment with ifosfamide, carboplatin and etoposide (ICE). The participants received ifosfamide 1800 mg/m2/day for 5 days, carboplatin 400 mg/m2/day for 2 days and etoposide 100 mg/m2/day for 5 days with rhIL-11 administered subcutaneously (s.c.) at 25-125 mug/kg/day on days 6-33.Forty-seven patients were studied. They ranged in age from 0.7 to 26 years, with a median age of 10.5 years. The median days to absolute neutrophil count >=0.5 x 109/l, platelet count >=50 x 109/l and platelet transfusions were 23, 18, 18, 16.5 and 18.5, 21, 20, 18 and 3, 3, 4, and 2 d at doses 25, 50, 75 and 100 mug/kg respectively.There was a dose-dependent increase in Cmax (7.6-25.5 ng/ml), AUC0-rho (57-209 ng.h/ml) and T1/2 (4-8.2 h) respectively. There was a 4% incidence of anti-IL-11 antibody formation. Clinically important adverse events to rhIL-11 were papilloedema and periosteal bone formation.Researchers concluded that rhIL-11 was well tolerated at doses of <=50 mug/kg (maximal tolerated dose) and associated with improved haematological recovery and reduced platelet transfusion requirements compared with historical controls receiving similar ICE chemotherapy without rhIL-11.(Source: Br J Haematol V 128 N 1 P 49-58 8 January 01, 2005.)